Globally, myocardial infarction is the primary cause of death among cardiac patients, needing the urgent development of new approaches in the fields of tissue engineering and regenerative medicine. From a tissue engineering perspective, novel cardiac 3D culture models of high physiological relevance are key to accelerate our understanding of human heart diseases and our ability to rapidly screen potential new drugs, thereby leading to new personalized treatments. Although in vitro preclinical models for cardiovascular disease have been reported, they still do not entirely recapitulate the important features of the native cardiac tissue. In the last decade, one of such platforms called human Engineered Heart Tissues (EHT) have emerged as affordable in vitro models for cardiac research. In EHTs, cardiac cells are embedded in a soft hydrogel material, then introduced in a microfluidic platform for cell culture under controlled conditions to prompt the formation of cardiac tissue, which in turn can be used as a model to study cardiovascular diseases and to test new treatments. Despite the progress achieved, traditional hydrogels used in EHT are inherently non-conductive and thus non-ideal as scaffolds, which limits the physiological relevance and applicability of these models.
The RHYTHM project was designed to address this challenge by developing bioinspired conductive hydrogels that replicate the physiological microenvironment that native cells find in cardiac tissue. These new hydrogels serve as soft, biocompatible scaffolds capable of conducting electrical signals, an essential feature for maintaining synchronized heart contractions in these artificial tissues. The main scientific objective of this project was to develop a biomaterial-based platform for applications in cardiovascular disease modelling. We aimed to develop a bioinspired injectable hydrogel scaffold with conductive properties to provide a more favorable microenvironment for cardiac tissue formation. Our approach was to synthesize self-assembled ion-conductive guanosine-quadruplex (GQ) hydrogels, which were then tested in the fabrication of advanced EHT platforms.
By integrating biomaterials science, microfabrication technologies, and cell biology, RHYTHM sought to establish a foundation for next-generation in vitro cardiac tissue models that bridge the gap between traditional cell culture systems and in vivo models. As such, this project contributes to the EU’s Horizon Europe goals of advancing health research, reducing the need for animal testing, and accelerating the development of safe and effective therapies for heart disease.
